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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 8/2011

01-12-2011 | Research Paper

Glycolysis inhibition by 2-deoxy-d-glucose reverts the metastatic phenotype in vitro and in vivo

Authors: Joseph L. Sottnik, Janet C. Lori, Barbara J. Rose, Douglas H. Thamm

Published in: Clinical & Experimental Metastasis | Issue 8/2011

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Abstract

Metastasis is the primary cause of death from many tumors, and novel anti-metastatic therapies are necessary. Recently, we showed that metastatic tumors down-regulate key oxidative phosphorylation (OXPHOS) genes in favor of glycolysis, a further enhancement of the Warburg effect. Therefore, we sought to determine if restriction of glycolysis using 2-deoxy-d-glucose (2DG) would lead to increased utilization of OXPHOS and inhibition of the metastatic phenotype. Noncytotoxic concentrations of 2DG dose-dependently inhibited in vitro migration and invasion in the highly metastatic DLM8-luc-M1 osteosarcoma (OS) cell line, as well as other metastatic human, canine, and murine cancer cells of different histotypes. This was associated with cytoskeletal rearrangement and inhibition of cathepsin L expression. A dose-dependent shift toward OXPHOS was confirmed by demonstrating increased oxygen utilization and decreased lactate production in 2DG treated cells. Finally, 2DG treatment significantly delayed metastasis and prolonged survival in an orthotopic postsurgical OS model. In conclusion, this work suggests that forcing cells away from glycolysis may inhibit key components of the metastatic phenotype, providing a novel avenue for metastasis prevention.
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Metadata
Title
Glycolysis inhibition by 2-deoxy-d-glucose reverts the metastatic phenotype in vitro and in vivo
Authors
Joseph L. Sottnik
Janet C. Lori
Barbara J. Rose
Douglas H. Thamm
Publication date
01-12-2011
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 8/2011
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-011-9417-5

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